2. Academic Validation
  3. Mechanism of CXCL8 regulation of methionine metabolism to promote angiogenesis in gliomas

Mechanism of CXCL8 regulation of methionine metabolism to promote angiogenesis in gliomas

  • Discov Oncol. 2024 Nov 2;15(1):614. doi: 10.1007/s12672-024-01467-2.
Jie Chang 1 2 3,  Yi Pan 1 2 3,  Fengfeng Jiang 4,  Wenxia Xu 1 2 3,  Yue Wang 5,  Lude Wang 6 7 8,  Bin Hu 9
Affiliations

Affiliations

  • 1 Central Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.
  • 2 Precision Diagnosis and Treatment Center, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.
  • 3 Key Laboratory of Nutrition and Metabolism Research for Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.
  • 4 Neurological Surgery Department, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.
  • 5 Dian Diagnostics Group Co. Ltd, Hangzhou, China.
  • 6 Central Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China. wangruth123@163.com.
  • 7 Precision Diagnosis and Treatment Center, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China. wangruth123@163.com.
  • 8 Key Laboratory of Nutrition and Metabolism Research for Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China. wangruth123@163.com.
  • 9 Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China. hubin_JH@163.com.
PMID: 39488622 DOI: 10.1007/s12672-024-01467-2
Abstract

Background: Gliomas are the most common malignant brain tumors characterized by angiogenesis and invasive growth. A detailed understanding of its molecular characteristics could provide potential therapeutic targets. In the present study, we sought to explore the key gene CXCL8 in methionine metabolism in gliomas and its potential role in angiogenesis.

Methods: U251 glioma cells were divided into control and methionine-restriction tolerant (constructed with 1/4 of the standard level of methionine in the culture medium) groups for transcriptome and metabolome analysis. To confirm the functions and mechanism of CXCL8 in glioma, heat map, volcano map, Go enrichment, gene set enrichment analysis (GSEA), protein-protein interaction network analysis, RT-PCR, western blotting assays, chicken embryo chorioallantoic membrane (CAM) test, chicken embryo yolk sac membrane (YSM) test and transplantation tumor nude mice model were performed. The TCGA database, CGGA database and clinical tissue samples were used to analyze CXCL8's significance on prognosis for patients with glioma.

Results: CXCL8 expression was significantly up-regulated in methionine-restricted tolerance cells, it also activated vascular system development and triggered angiogenesis. CXCL8 expression is negatively correlated with survival prognosis in gliomas.

Conclusions: Glioma cells promote angiogenesis in methionine-restricted environments through the activation of CXCL8, compensating for nutrient deprivation, and possibly contributing to the failure of antiangiogenic therapy.

Keywords

Angiogenesis; CXCL8; Glioma; Methionine metabolism.

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